The purpose of this FOA is to solicit applications for
Clinical Trials Units (CTUs) for NIAID clinical research networks focused on
the following six research areas: 1) Adult HIV therapeutic strategies,
including HIV cure, noninfectious comorbidities, and the infectious
comorbidities of hepatitis and tuberculosis; 2) strategies to address HIV and
HIV-associated infections in pediatric and maternal populations; 3)
integrated HIV prevention strategies; 4) microbicide strategies to prevent
HIV infections; 5) vaccines to prevent HIV infections; and 6) strategies to
address antibacterial resistance.

Key Dates

Posted Date

April 10, 2012

Letter of Intent Due Date

December 29, 2012

Application Due Date(s)

January 29, 2013

AIDS Application Due Date(s)

Not Applicable.

Scientific Merit Review

July, 2013

Advisory Council Review

January, 2014

Earliest Start Date(s)

May, 2014

Expiration Date

January 30, 2013

Due Dates for E.O. 12372

Not Applicable.

Required Application Instructions

It is critical that applicants follow the instructions in
the PHS398
Application Guide except where instructed to do otherwise (in this FOA or
in a Notice from the NIH Guide
for Grants and Contracts). Conformance to all requirements (both in
the Application Guide and the FOA) is required and strictly enforced. While
some links are provided, applicants must read and follow all application
instructions in the Application Guide as well as any program-specific
instructions noted in Section IV. When
the program-specific instructions deviate from those in the Application Guide,
follow the program-specific instructions. Applications that do not
comply with these instructions may be delayed or not accepted for review.

The purpose of this FOA is to solicit applications from
domestic and foreign institutions to serve as Clinical Trials Units (CTUs) for
NIAID clinical research networks focused on the following six research
areas:

2. Strategies to address HIV and HIV-associated infections
in pediatric and maternal populations;

3. Integrated HIV prevention strategies;

4. Microbicide strategies to prevent HIV infection;

5. Vaccines to prevent HIV infection; and

6. Strategies to address antibacterial resistance.

The establishment of a Clinical Research Network on
Antibacterial Resistance presents a new opportunity for NIAID to leverage
HIV/AIDS CTUs and Clinical Research Sites (CRSs) to expand clinical research on
the pressing problem of antibacterial resistance.

The development, implementation and adaptation, as needed,
of the clinical research program of each clinical research network will be
managed through separate awards to establish and maintain Leadership Groups
(LGs). The NIAID has previously solicited applications for Leadership
Groups through separate FOAs.
Each Leadership Group (LG) will be comprised of a Leadership and Operations
Center (LOC), a Laboratory Center (LC), and a Statistical and Data Management
Center (SDMC). The association of the CTUs and their CRSs along with the
LG will constitute the clinical research network. NIAID expects to fund a
minimum of 25 CTUs in order to support the research agendas of the clinical
research networks.

The CTU is the nucleus of clinical research activity for the
clinical research networks. It is an organization/institution responsible for
the coordination and execution of clinical trials in accordance with clinical
research network, NIAID and other applicable policies. The CTU is composed of
multiple components including:

1. CTU administrative office

2. At least one, but no more than eight (8) domestic or
international CRS(s)

3. Community Advisory Board(s) (CABs)

4. Pharmacy(ies)

5. Laboratory(ies)

6. Other clinical research activities (including but not
limited to data management, quality management, regulatory assurance and
training)

The CTU provides the scientific and administrative expertise
as well as the infrastructure to participate in two or more NIAID HIV/AIDS clinical
research networks. CTUs
may also propose to be part of the Clinical Research Network on Antibacterial
Resistance, but such affiliation is not required. Each CTU
must demonstrate sufficient breadth and depth of scientific expertise to
contribute to the ongoing refinement of the clinical research network(s)
agenda, participate in an array of scientific studies, and demonstrate a
productive partnership with the community(ies) in which they propose to conduct
research. The CTU Administrative Office is responsible for managing all
CTU resources and overseeing the performance of its associated components
including CRS(s), local laboratory and pharmacy functions as defined
below. A CRS is a component of a CTU and is defined as a discrete
location (e.g. hospital, outpatient clinic, community health center, private
practice, local health department clinic) with appropriate, identified and
characterized potential trial participants (e.g. demographics, incidence and
prevalence of HIV/AIDS) where participant recruitment and retention, protocol
management and other clinical research activities are conducted.

A priority
is placed on reaching populations severely impacted by the HIV/AIDS epidemic
whose participation will help address priorities for NIAID HIV/AIDS research.
These populations include, but are not limited to women, adolescents and
minorities in the United States as well as populations in low and middle-income
countries. CTUs with the flexibility and capability to conduct multiple
clinical research projects, the ability to respond rapidly to evolving research
opportunities, and the capacity to participate in the development and
implementation of the clinical research plans of multiple NIAID clinical
research networks are particularly sought.

2. Background

Over the past 30 years, HIV/AIDS research has led to
phenomenal scientific advances. Scientists uncovered the structure and genetic
organization of HIV and began to understand the mechanisms by which HIV causes
disease. This understanding led to the development of (i) tests to detect HIV
infection, measure HIV viral load, and monitor immune function, and (ii) highly
active antiretroviral therapies (HAART).

Despite these scientific advances, according to the Joint
United Nations Programme on HIV/AIDS (UNAIDS) 34 million people
globally are estimated to be living with HIV, and 22.5 million of these are
living in sub-Saharan Africa. Slightly more than half of all people living
with HIV are women and girls. In sub-Saharan Africa, more women than men are
living with HIV, and young women aged 15–24 years are as much as eight times
more likely than men to be HIV-infected. HIV/AIDS continues to be responsible
for approximately two million deaths each year.

Researchers from the CTUs and associated CRSs have supported
the development of NIAID-funded HIV/AIDS clinical research networks and their
diverse agendas. The success of the networks to date has relied heavily on the
scientific expertise and leadership contributions of the CTUs and associated CRS
personnel.

The NIAID currently directly funds 72 CTUs comprised of
approximately 160 CRSs worldwide. Each CTU participates in one to five of the
existing six HIV/AIDS clinical research networks, and collectively have
enrolled over 74,000 participants in Phase I, Phase II, Phase IIb, and Phase
III observational and interventional studies through November 1, 2011. The CRS
distribution has been predominantly reflective of the communities most heavily
impacted by the HIV/AIDS epidemic.

CRSs have recruited participants from diverse populations to
support the research agenda of the NIAID HIV/AIDS clinical research networks.
By November 1, 2011, the current CRSs had enrolled over 20,000 participants
into HIV pediatric and adult therapeutic studies in 20 countries. Data
generated from these studies have contributed to the development of
international guidelines for HIV treatment and have improved the clinical
management of HIV infection and its co-morbidities. CRSs have also enrolled
over 6,700 participants into HIV vaccine prevention studies in 11 countries. In addition, CRSs have enrolled over
10,000 participants into microbicide HIV prevention studies and over 8,000
participants into other non-vaccine HIV prevention studies which led to the
successful development of integrated, behavioral and biomedical prevention
models.

Many CRSs have
been able to effectively enroll and retain participants in large multi-center
clinical trials. For example, one significant microbicide study titled, “Phase
II/IIb Safety and Effectiveness Study of the Vaginal Microbicides BufferGel and
0.5% PRO 2000/5 Gel (P) for the Prevention of HIV Infection in Women” (HPTN 035),
evaluated the effectiveness of two topical microbicides, BufferGel and 0.5% PRO
2000 compared to placebo gel and a no-gel study arm. This Phase II/IIb
clinical trial was conducted at 9 CRSs in Africa and the US and over 3,000
participants were enrolled with a retention rate of 94%.

The CTUs have contributed to several high- impact, ground
breaking research studies. For example, the study titled, “A Randomized Trial
to Evaluate the Effectiveness of Antiretroviral Therapy Plus HIV Primary Care
versus HIV Primary Care Alone to Prevent the Sexual Transmission of HIV-1 in
Serodiscordant Couples” (HPTN 052) evaluated
the treatment and prevention benefits of early versus standard initiation of
ART among serodiscordant couples in 8 countries in Africa, Asia, and South
America. The study revealed a 96% benefit in preventing HIV infection of the
uninfected partner when the infected partner initiated ART immediately compared
to these who delayed ART.

The CTUs have been able to respond rapidly to emerging needs
of the clinical research networks. For example, in 2009, NIAID, through the
IMPAACT network, quickly initiated two clinical studies enrolling over 200 participants in 3 months, that determined that the 2009 H1N1
influenza vaccine could safely elicit a protective immune response in
HIV-infected pregnant women and children.

The CTUs have also been effective in engaging constituents
representing the needs and research priorities of the communities that they
represent primarily through the use of Community Advisory Boards (CABs) working
with the CRSs. CABs consist of volunteer representatives from the communities
in which the research is conducted. During the stages of protocol development,
implementation and close-out, CTUs actively engage their CABs and other
community stakeholders in dialogue to ensure that the protocols are
representative of and reflect the priorities and needs of their communities.

In summary, the CTUs have played a significant role in
HIV/AIDS clinical research in the areas of both treatment and prevention. The
accomplishments of the CTUs have contributed to improved clinical management of
HIV infection throughout the world through the identification of more effective
therapies and treatment strategies, as well as new strategies to prevent the
spread of HIV.

3. CTU Structure and Function

Clinical
Trials Units. Clinical Trials Units provide the scientific and
administrative expertise as well as the infrastructure to support the NIAID
clinical research networks. A CTU is an organization/institution composed of
multiple components, including:

CTU administrative office

At
least one, but no more than eight (8) domestic or international CRS(s)

Community Advisory Board(s)

Laboratory(ies)

Pharmacy(ies)

Other clinical research activities (including but not limited to
data management, quality management, regulatory assurance and training)

The
CTU must reflect a cohesive, integrated unit and participate in at least two
NIAID HIV/AIDS clinical research networks. An optimal CTU
configuration will support participation in multiple clinical research
networks, promote efficient utilization of resources and infrastructure, and
include continuous performance evaluation. The CTU will assume the network
affiliations of its component CRSs.

In
addition, CTUs may participate in the Clinical Research Network on
Antibacterial Resistance, but such participation is not required.

The CTU must
have sufficient space (facility), dedicated staff and institutional commitment
to ensure organizational stability and fulfill the CTU’s objectives. The CTU
composition including the location of the CTU administrative office, location
of CRS(s), number of CRS(s), scope and complexity must be commensurate with the
scientific diversity and the clinical research networks in which the CTU
proposes to participate. The NIAID recognizes that the scientific
contributions of the CTU Principal Director/Principal Investigator
(PD(s)/PI(s)), CRS Leaders, and Investigators are essential in developing and
carrying out a strong, high priority research agenda for each clinical research
network. If there are multiple PD(s)/PI(s), the level of effort of each PD/PI
must be commensurate with the size and scope of the CTU. The CTU PD(s)/PI(s)
is/are responsible for all CTU activities and CTU performance, and may also
serve as the primary scientific and administrative representative(s) to the
clinical research network(s). The CTU is expected to coordinate and
collaborate with the LOCs to ensure performance monitoring and evaluation of
sites. The day-to-day operations
of the CTU must be overseen by a CTU Coordinator with relevant management and
clinical research experience and qualifications.

CTU
Administrative Office. The CTU Administrative Office provides
oversight, coordination, fiscal management, and administrative support for all
activities of the CTU. CTU Administrative Office staff may also contribute to
the clinical research network agenda and priorities through activities such as
scientific and resource committee membership or protocol team membership.

Clinical
Research Site. A Clinical Research Site (CRS) is a component
of a CTU and is defined as a discrete location (e.g. hospital, outpatient
clinic, community health center, private practice, local health department
clinic) with appropriate, identified and characterized potential trial
participants (e.g. demographics, incidence and prevalence of HIV/AIDS) where
participant recruitment and retention, protocol management and other clinical
research activities are conducted. The CRS must be staffed by qualified
professionals capable of conducting clinical research for one or more clinical
research networks in accordance with Good Clinical Practice (GCP), local regulatory
requirements, and other applicable NIH requirements. In
addition, each CRS
must participate in one or more NIAID HIV/AIDS clinical research network(s).
The activities of each CRS will be directed by a CRS Leader with the experience
and qualifications to oversee clinical activities and the day-to-day clinic
operations will be overseen by a CRS Coordinator with relevant clinical
research experience and qualifications. An
individual CRS and/or CRS Leader may be proposed in only one CTU application.

The number of CRSs at any one institutional location (e.g.
hospital or medical campus) should be limited to the number required to provide
appropriate and cost-effective clinical research oversight for diverse
populations (e.g. pediatrics, adult medicine). However, it is expected that
each institutional location will have no more than one CRS for each of the
diverse populations. Where practical and efficient, applicants are encouraged
to combine the operations of diverse populations into one CRS.

In addition to the CRSs listed in the application, there may
be future opportunities to bring on limited protocol-specific (PS) sites to
meet the needs of a particular protocol during the project period. These PS
sites will be identified by the clinical research network, CTU, or NIAID to
meet a discrete need; for example, to accomplish protocol-specific recruitment
goals, if the capacity does not exist at currently funded CRSs. These PS sites
will be scheduled to close, and funding discontinued, upon completion of the
specified protocol activities, unless the clinical research network requires
the PS site to meet additional, identified, appropriate protocol activities. Protocol-Specific
sites should not be named in this application. Protocol-specific sites will be
identified and proposed after award, based on identified protocol-specific
clinical research network needs.

Community
Advisory Board(s) (CABs). Each CTU must develop and implement
a plan for forming and maintaining a productive partnership in the communities
in which clinical research will be conducted. This partnership may be
facilitated through a CAB. A CAB is an active group of individuals
representing the local population(s) impacted by HIV/AIDS. The organization and
composition of each CAB should reflect local community representation, promote
community engagement, and provide local perspective(s) on the implementation of
the NIAID clinical research plan(s). The CTU must determine how best to
organize community partnerships to meet the research needs and priorities of
the local population. This may include multiple CABs if required to enable
effective representation of the populations involved, for example, to represent
geographically, culturally, or other distinct populations.

Considering the overall CTU budget, CTUs shall provide
support, including but not limited to reasonable costs for CAB meetings and
associated expenses. CTUs will also be expected to provide reasonable
accommodation, access to trainings, local engagement activities and other means
of educating and/or engaging the CAB and community at large.

Laboratory.
Each Leadership Group (LG) has a network laboratory center (LC) which leads the
laboratory activities that are required to carry out the clinical research
network agenda. In addition, each CRS must have access to a local laboratory
capable of protocol-specified testing, as well as specimen processing,
laboratory data management capabilities, shipment and storage of samples
collected at the CRS. The local laboratory must be capable of communicating
efficiently with the network LC. The CTUs may elect to utilize as appropriate,
local laboratory services such as hospital clinical pathology departments and
commercial laboratories, or provide laboratory services within the CTU. When
practical and efficient, CTUs may utilize a single laboratory to support
multiple CRSs. Laboratories must meet and maintain specific requirements to
ensure compliance with Good Clinical Laboratory Practice (GCLP).

Pharmacy.
Each CRS must have access to a secure pharmacy facility staffed by qualified
pharmacist(s) in order to receive, store, manage inventory, dispense study
product, and maintain accurate records in accordance with GCP, applicable
United States regulations, NIAID guidelines and local requirements/regulations.
The CTUs may elect to utilize appropriate pharmacy services, such as a research
pharmacy operated by a medical facility, or provide pharmacy services within
the CTU. When practical and efficient, CTUs may utilize a single pharmacy to
support multiple CRSs. The Pharmacist(s) of Record (PoR) is/are responsible
for overseeing all pharmacy-related activities.

Other
Clinical Research Activities.

Regulatory
Assurance. Each CRS must have an efficient process to ensure
compliance with all applicable regulatory requirements.

Data
Management. Each clinical research network has a Statistical
and Data Management Center (SDMC) responsible for the overall data management
activities of the clinical research network. In addition, each CRS must have
access to a local data management facility capable of effectively and
efficiently communicating with the SDMC. The local data management facility
must accurately collect, manage, and report clinical research data from the
CRSs in accordance with GCP,
NIAID, and clinical research network requirements. When practical and
efficient, CTUs may utilize a single data management facility for multiple
CRSs.

Quality
Management. Each CRS must also have a system for conducting
internal quality control and quality assurance, consistent with NIAID clinical
research policies and SOPs.

Staff
Training. Each CRS must have adequately trained and
experienced personnel to conduct all required clinical research activities. In
addition, each CRS must have a process for ongoing assessment and delivery of
training to ensure staff have the appropriate knowledge and qualifications to
perform required activities in accordance with GCP, NIAID, and clinical
research network requirements.

4. Core and Protocol Funds

Funding to carry out the network’s clinical research
agendas falls into two categories:

1. Core
Funds. NIAID will provide core funds directly to the CTUs on
an annual basis to support the Administrative Office and other CTU components.
Each CTU will receive core funding at a level sufficient to maintain a limited
staff and infrastructure. CTU core funds will be determined by NIAID based
upon the size and scope of the funded CTU. For example, a CTU participating in
2-3 NIAID HIV/AIDS clinical research networks and comprising 3-4 CRSs may
expect core funding within the range of $1.2M-$2.0M total costs. The amount
will be adjusted based on the size/scope of the CTU.

Core funds include (but are not limited to) minimal support
for the following activities:

CTU PD(s)/PI(s) to maintain CTU administration and an ongoing
contribution to clinical research network science

Core funds are not intended to cover 100% of these
expenses. Core funds do not include expenses directly attributable to the
development, approval, or conduct of specific clinical trials. CTU core funds
will be supported by NIAID funds; however, applicants are encouraged to develop
collaborations to enhance utilization of existing resources.

Core funds will be provided at the time of award.

2. Protocol
Funds (PF). This category of funding provides additional
support to the CTU to cover protocol-related expenses attributable to protocol
development, implementation or close-out of a clinical trial.

Following discussions between the NIAID and the network LOC,
the NIAID will determine the amount of PF required to support each CRS’s
participation in an approved protocol.

Protocol funds include (but are not limited to) the following protocol-specific expenses:

Salary for additional staff or expanded commitment of core staff

Participant recruitment and retention

Protocol required tests and evaluations

Participant reimbursement

Equipment and supplies

Community education and engagement structures and activities

Additional support for regulatory, pharmacy, data management, and
laboratory activities

When it is determined that the PF is needed in addition to
core funds to carry out the clinical research network’s research agenda, funds
may be distributed by one of the following:

Route 1: The NIAID will disburse the PF directly into the CTU
grant awards.

Route 2: The NIAID will disburse the PF into the Leadership
Group (LG) LOC grant award for the LOCs to disburse to the participating CTUs.

Each CTU applicant must be able to administratively
accommodate both routes for PF distribution in their financial management
structure to ensure prompt and efficient budget allocation to their component
CRSs. If the clinical research network uses route 2 above for PF distribution,
the CTU PD(s)/PI(s), in consultation with the CRS and NIAID, will determine
whether the CRS is capable of receiving PF directly from the LOC or whether the
PF will be routed through the CTU Administrative Office to the CRS.

The CTU Administrative Office has primary responsibility for
PF accounting for all CTU components, regardless of the method of PF
distribution, and is responsible for providing funding information to the NIAID
and the affiliated clinical research network(s).

Protocol funding will be determined post-award and should
not be requested in response to this FOA.

For
those CTUs also proposing affiliation with the Clinical Research Network on
Antibacterial Resistance, protocol funding will be disbursed directly from
NIAID into the CTU grant awards. In addition, for some clinical research, CTUs
may receive protocol funds directly from the Antibacterial Resistance
Leadership Group.

Section
II. Award Information

Funding Instrument

Cooperative Agreement

Application Types Allowed

New
Renewal

The OER
Glossary and the PHS398 Application Guide provide details on these application
types.

Funds Available and Anticipated Number of Awards

NIAID intends to commit up to an estimated total cost
of $70M in FY 2014.

Award Budget

Application budgets are not limited, but need to reflect
actual needs of the proposed project based on the size/scope of the CTU. For
example, a CTU participating in 2-3 NIAID HIV/AIDS clinical research networks
and comprising 3-4 CRSs may expect core funding within the range of
$1.2M-$2.0M total cost..

Award Project Period

The maximum period is 7 years.

NIH grants policies as
described in the NIH
Grants Policy Statement will apply
to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH
Grants Policy Statement, are allowed.

Required Registrations

Applicant organizations must complete the following registrations
as described in the PHS398 Application Guide to be eligible to apply for or
receive an award. Applicants must have a valid Dun and Bradstreet Universal
Numbering System (DUNS) number in order to begin each of the following
registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.

All registrations must be completed by the application due
date. Applicant organizations are strongly encouraged to start the registration
process at least 4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA
that is essentially the same as one currently pending initial peer review
unless the applicant withdraws the pending application. NIH will not accept any
application that is essentially the same as one already reviewed.

Applications proposing participation in
fewer than two NIAID HIV/AIDS clinical trials networks will not be responsive
and therefore not reviewed.

Applications proposing more than eight CRS will not be
responsive and therefore not reviewed.

Each CRS may be proposed in only one CTU application.

A CTU PD/PI may only be proposed in one CTU application.

Section
IV. Application and Submission Information

1. Address to Request Application Package

Applicants are required to prepare applications according to
the current PHS 398 application forms in accordance with the PHS 398
Application Guide.

2. Content and
Form of Application Submission

It is critical that applicants follow the instructions in
the PHS398
Application Guide, except where instructed in this funding opportunity
announcement to do otherwise. Conformance to the requirements in the
Application Guide is required and strictly enforced. Applications that are out
of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review workload and
plan the review.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

Applications must be prepared using the PHS 398 research
grant application forms and instructions for preparing a research grant
application. Submit a signed, typewritten original of the application,
including the checklist, and three signed photocopies in one package to:

Detailed
Budget for Initial Budget Period. Proposed budgets for the
first Year for core costs only, not any requests for protocol funds (PF).

Budget
for Entire Proposed Period of Support This is the Composite
Budget for all years of Proposed Support.

Budgets
Pertaining to Consortium/Contractual Arrangements Detailed
Budgets for Consortium Agreements should be provided as a separate page and
summed as a line item on PHS 398 Form Page 4.

Research
Plan

Specific Aims for the entire CTU

Note:
For each component below, include a Cover Page and other information as
described under detailed component headings. Do not use PHS 398 Form Page 1
for individual components.

Component 1. CTU Research Overview

Component 2. CTU Administration

Component 3. Financial Resource Management

Component 4. Communication

Component 5. Evaluation

Component 6. Community

Component 7. Pharmacy

Component 8. Laboratory

Component 9. Other Clinical Research Activities

Component 10. Clinical Research Site(s) (CRS)

NOTE: label each individual CRS described with a number
and letter combination (10A, 10B, 10C, etc.).

Component 11. Clinical Research Network on Antibacterial
Resistance

Biographical
Sketch (Biographical Sketch Format Page). Provide
biographical sketches of all senior/key professional personnel for all
components at the end of the application. Place PD(s)/PI(s) biographical
sketch first, followed by those of other key personnel (CTU Coordinator, CRS
Leader, CRS Coordinator, Pharmacist(s) of Record) in alphabetical order.

Resources. Complete the resources available for each component.

Checklist

Appendix

Component 1. CTU Research
Overview

Research
Strategy (Limited to 30 pages): Organize this section in the
order specified in the PHS 398 Instructions Section 5.5.3. Make sure to start
this component with the appropriate section heading in order, addressing
Significance, Innovation, and Approach, including the appropriate information.

Summarize the proposed scope of research to support the
scientific priorities of the clinical research networks the CTU is proposing to
join. Describe (i) the potential trial participants the CRS(s) can access
(e.g., demographics, incidence and prevalence of HIV/AIDs); (ii) the proposed
approach to integrating functions within each of the scientific areas proposed
and across the entire CTU; and (iii) how the CTU will position itself to
respond to emerging scientific priorities of proposed clinical research
networks.

Performance
and Applicant Experience. Within the Approach section, for renewal applications,
(i) expand upon past performance of the CTU over the previous 5 to 7 years;
(ii) identify strengths and areas for improvement; and (iii) provide
improvement plans. For new
applications, provide the information identified above related to a
clinical trials program of similar scope and complexity in this area of
research during the past 5 to 7 years.

Provide a table as shown below with relevant information
including the name of the CTU PD(s)/PI(s), name of each proposed CRS, the CRS
leader and identify each CRS network(s) affiliation.

CTU PD(s)/PI(s) (1 or more)

CRS Name

CRS Leader (1 per CRS)

Clinical Research Network on Therapeutics for HIV/AIDS and
HIV-associated Infections in Adults

Clinical Research Network on HIV/AIDS and HIV-associated
Infections in Pediatric and Maternal Populations

Clinical Research Network on Integrated Strategies to
Prevent HIV Infection

Clinical Research Network on Microbicides to Prevent HIV
Infection

Clinical Research Network on Vaccines to Prevent HIV
Infection

CRS 1

Dr. A

X

X

CRS 2

Dr. B

X

CRS 3

Dr. C

X

X

CRS 4

Dr. D

X

X

X

X

X

Scientific
Leadership. (i) Identify PD(s)/PI(s) and other relevant CTU scientific leadership. (ii) Describe the scientific experience and knowledge of the PD(s)/PI(s),
CRS Leader(s), and Investigator(s) including relevant contributions to the
field(s) of research proposed. (iii) Provide justification for proposed PD(s)/PI(s).
(iv) Describe how scientific leadership will be provided within the CTU and to
the NIAID clinical research networks. Summarize the proposed approach to
making high level scientific decisions including selection of protocols, as
well as reassessment and redirection of resources to support the scientific
priorities of the proposed network(s). (v) Describe the plan for CTU staff to contribute to the development of the network clinical research plans through
activities such as membership on protocol teams, scientific and resource
committees, and scientific review of proposed concepts and protocols.

Applicants are encouraged to draw upon their past
experiences with participation in HIV/AIDS multicenter clinical trials or
equivalent experience.

Component 2. CTU Administration (Limited to 12 pages)

Structure
and Governance

Organizational
Structure. (i) Provide an organizational chart describing the
overall CTU structure which demonstrates a cohesive, integrated approach to
supporting the scientific priority areas of the NIAID HIV/AIDS clinical
research networks for which the CTU is proposing to participate; include
detailed description of lines of authority. (ii) Provide a CTU staffing plan,
including, but not limited to, the following ‘Key Personnel’: CTU PD(s)/PI(s),
CTU Coordinator, CRS Leader(s), CRS Coordinator(s) and Pharmacist(s) of Record.
(iii) Describe proposed approaches to efficient utilization of resources and
infrastructure, avoidance of redundancies, resource sharing strategies, and
cost containment measures which support the proposed CTU configuration.

Scientific Leadership Diversity. Briefly describe how
diversity is promoted and encouraged within the CTU/CRS scientific leadership
to reflect the diversity of the populations from which participants are
recruited.

Institutional
Commitment/Support

Describe (i) the available institutional research, clinical,
laboratory and administrative space and administrative positions to support the
CTU; (ii) other strategies to defray the total costs of CTU operations; (iii)
institutional discretionary funds, if any (e.g., philanthropic funds, clinical
revenues) under the control of or otherwise accessible to the PD(s)/PI(s) for
the CTU to ensure adequate staffing and resources during periods where protocol
activity and associated NIAID funding is low.

Component 3. Financial Resource Management (Limited to 6 pages)

Describe (i) the financial management structure, including
the duties, responsibilities, experience, and time commitment of essential
staff; (ii) policies and procedures for establishment and implementation of
consortia agreements, including timelines and responsible parties; (iii) prior
experience managing complicated funding streams; (iv) how resource utilization
will be monitored and adjusted as needed; (v) the process for allocating
resources to each CRS in a transparent manner; (vi) the plan to provide timely
financial status information to the LOC and NIAID, including all funding
sources to the CRSs; (vii) criteria used to determine whether CRSs have the
capability to receive protocol funds directly from the LOC, and (viii) which
CRSs, if any, have the ability to receive protocol funding directly from
clinical research networks (refer to Part II, Section 1.4 for description of
both funding models).

Describe (i) the process including metrics and frequency for
assessing operational performance and capacity of all components of the CTU and
reporting relevant information to the NIAID and the clinical research network;
(ii) how improvements in performance will be achieved; (iii) the process for
assessing and evaluating potential PS sites; (iv) how CRSs will be prepared for
protocol implementation including responsible parties; and (v) close-out
procedures for poorly performing CTU components.

Component 6. Community (Limited to 12 pages)

Describe (i) plans for community engagement including
organizational charts; (ii) the role of CAB(s) and how the CAB(s) will support
all CRS(s) and their populations(s); (iii) existing relationships between the
CRS and community(ies) in which the research will be conducted; include
information on nature and length of relationship as well as any outreach
conducted to date; (iv) dedicated staff from the CRS, if any, that will support
community activities and a description of their roles and responsibilities; (v)
CAB composition including process for elections, jurisdiction, representation,
function, work products, resource requirements; (vi) the plans for training CAB
members including mentoring and continuing education; and (vii) communication
with the CTU Administrative Office and the CRS; and (viii) the process for
determining the level of financial support that will be provided by the CTU for
CAB activities and how that level of support will be reassessed throughout the
project period.

Component 7. Pharmacy (Limited to 12 pages)

Organizational
Structure. Describe (i) the overall pharmacy structure
including a detailed description of lines of authority; specify which (if any)
activities are centralized; a diagram showing the roles and relationships of
each pharmacy is recommended and should reflect how the pharmacist(s) (or
equivalent) will be integrated into CTU organization and management; (ii) the
duties and responsibilities of essential pharmacy personnel; include a short
summary of the experience, expertise and certification, if applicable, and (iii)
describe the level of effort of essential pharmacy personnel (the level of
effort must be commensurate with the size and scope of the CTU).

Facilities
and Equipment. Describe (i) the pharmacy facilities including
location, infrastructure, equipment (e.g. refrigerators, freezers, temperature
monitoring system, power generator(s)), other specialized equipment, storage,
systems for security, inventory or other key processes; (ii) and identify which
CRSs the pharmacy facilities will support; (iii) any specialized capabilities
available in the pharmacy locations(s); and (iv) the approach for optimizing
efficiencies to support proposed clinical research networks by resource
sharing, centralizing activities, implementing cost containment measures, or
other innovative approaches.

Pharmacy
Quality Management. Describe (i) the requirements and
processes for developing and implementing pharmacy Standard Operating
Procedures (SOPs); the approach for managing pharmacy activities including
study product receipt, storage, preparation, labeling, dispensing, final
disposition, record keeping and accountability; participant counseling
activities, if applicable; and (ii) how these processes support applicable laws
and regulations.

Performance
and Experience. Describe past pharmacy performance and
experience over the previous 5 to 7 years with U.S. FDA regulated research as
well as non-U.S. FDA regulated research and identify areas for improvement, if
any. Describe the approach for optimizing efficiencies to support proposed
networks by resource sharing, centralizing activities, implementing cost
containment measures, or other innovative approaches. List any applicable
pharmacy certifications and/or accreditations.

Component 8. Laboratory (Limited to 12 pages)

Organizational
structure. Describe (i) the plan for CTU staff oversight of
laboratory operations and communications, including staff roles and experience;
(ii) the overall laboratory structure including a detailed description of lines
of authority and identification of which CRSs the laboratory facilities will
support; a diagram showing the roles and relationships of each laboratory is
recommended; (iii) the duties and responsibilities of essential laboratory
personnel; include a short summary of the experience, expertise and
certification, if applicable; (iv) the plan for interactions with the clinical
research network Laboratory Center (LC); and (v) the level of effort of
essential laboratory personnel (the level of effort must be commensurate with
the size and scope of the CTU).

Laboratory
Quality Management. Describe (i) the requirements and
processes for developing and implementing laboratory SOPs; (ii) how these
processes support applicable laws and regulations; and (iii) challenges and
solutions for getting materials (e.g. test kits) into the country and specimens
out of the country (if applicable). Include any laboratory certification,
quality assurance or other applicable accreditation.

Performance
and Experience. Describe past laboratory performance and experience
over the previous 5 to 7 years with U.S. FDA regulated research as well as
non-U.S. FDA regulated research and identify areas for improvement, if any.
Describe the approach for optimizing efficiencies to support proposed networks
by resource sharing, centralizing activities, implementing cost containment
measures, or other innovative approaches.

Component 9. Other Clinical Research Activities (Limited to 12 pages)

Regulatory
Assurance. Describe regulatory requirements for protocol
approval and implementation. Include details of (i) national, central, or
local IRB and other regulatory requirements; (ii) past experience and average
timeline for protocol approval; (iii) challenges and other unique issues that
may have impacted protocol approval and implementation; and (iv) strategies to
overcome regulatory hurdles, if applicable.

Describe the plan for ensuring compliance with GCP, local,
national, and other applicable regulatory requirements. Include any unique
requirements, issues, previous experience, challenges, and a plan to
efficiently collaborate with local IRB or ethics boards to facilitate protocol
development and approval.

Data
Management. Describe (i) the overall data management structure
including a detailed description of lines of authority, and specify which (if
any) activities are centralized; (ii) the duties and responsibilities of
essential data management personnel including assurance of data quality; (iii)
the plan for effective interactions between the SDMC and local data management
facility; (iv) level of effort of all essential data management personnel (the
level of effort must be commensurate with the size and scope of the CTU); (v)
the current information technology (IT) infrastructure; and (vi) a plan for
ensuring data integrity and security including processes to monitor and
restrict access, and data back-up systems.

Quality
Management. Describe (i) the overall quality management plan
and structure for all parts of the CTU including a detailed description of
lines of authority; specify which (if any) activities are centralized; (ii) the
duties and responsibilities of essential quality management personnel; (iii)
the level of effort of all essential quality management personnel (the level of
effort must be commensurate with the size and scope of the CTU); and (iv) a
plan to perform ongoing day-to-day quality checks as well as retrospective,
objective, systematic, and periodic reviews of trial-related activities to
ensure compliance with protocols, GCP, and NIAID requirements. Include the
process, metrics, frequency of evaluation and documentation of findings, and
how modifications to quality management will be determined and implemented.

Staff
Training. Describe (i) how training needs (other than
protocol-specific training) will be assessed for all components of the CTU;
(ii) how training content will be developed/decided; (iii) how training needs
will be reviewed, evaluated, and modified; and (iv) plans for mentoring new
staff and providing continuing education for existing staff.

Bylaws,
policies, and standard operating procedures should not be included in the
application.

Label each individual CRS (up to 8) with the number and a
letter (10A, 10B, 10C, etc.) using the following outline as guidance:

Organizational
Structure. Describe (i) the overall CRS structure including a
detailed description of lines of authority; a diagram showing the roles and
lines of authority within each CRS is recommended , reflecting support
commensurate with the size and scope of the CRS; and; and (ii) the duties and
responsibilities of CRS Leader and other CRS personnel. The CRS leader is
considered ‘key personnel’, so a summary of their qualifications, experience
and level of effort should be provided on PHS 398 Form Page 2; however the
application may expand on the CRS Leader’s scientific and leadership expertise
as well as clinical research experience.

Facilities
and Equipment. Describe (i) the clinic facilities including
location, layout, infrastructure, equipment, vehicles, storage, and security
and backup systems or other key processes required for efficient, uninterrupted
clinical research; and (ii) any specialized capabilities available in the
location(s). It is not necessary to include items described in other
components.

Administration.
Describe (i) how activities will be coordinated across multiple clinical
research networks, if applicable; (ii) innovative approaches for optimizing
efficiencies to support proposed clinical research network(s); and (iii) the
approach for ensuring that protocol activities are conducted in accordance with
NIAID and all applicable regulatory requirements.

Performance
and Experience. Describe past performance and experience as a
CRS or equivalent over the previous 5 to 7 years, including, but not limited
to, types of studies conducted, enrollment and retention, data quality metrics,
and timeliness of protocol implementation and execution. Describe challenges
and any improvement plans (if applicable).

A
CTU proposing affiliation with the Clinical Research Network on Antibacterial
Resistance should NOT list relevant CRS(s) as a separate component in this
section of the application.

Applicants proposing participation with the Antibacterial
Resistance network should submit a brief capability statement describing
capacity and capability to perform clinical trials in antibacterial
resistance. Include evidence of: (i) ability to recruit and retain relevant
patient populations, including intensive care unit (ICU) and emergency room
patients; (ii) ability to identify, recruit, and manage appropriate sites for
antibacterial resistance clinical research or trials; (iii) ability to monitor
progress toward enrollment goals and adjust as needed, depending on changing
circumstances; and (iv) ability to support local laboratory activities and
pharmacy functions. Applicants are encouraged to draw upon their past
experiences with participation in antibacterial resistance, multicenter
clinical trials or equivalent experience.

Response
to this optional component will not affect the overall impact/priority score
for the application.

Letters of Support

Provide a letter signed by the appropriate institutional
official(s) from the grantee institution documenting specifics of institutional
commitment for this proposed award period.

Resource Sharing Plan

Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS398
Application Guide, with the following modification:

All applications, regardless of the amount of direct costs
requested for any one year, should address a Data Sharing Plan.

Appendix

Do not use the Appendix to circumvent page limits. Follow
all instructions for the Appendix (please note all format requirements) as
described in the PHS398 Application Guide.

Foreign Institutions

Foreign (non-US) Institutions must follow policies described
in the NIH
Grants Policy Statement, and procedures for foreign institutions described
throughout the PHS398 Application Guide.

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review and responsiveness by components of participating organizations,
NIH. Applications that are incomplete and/or nonresponsive will not be
reviewed.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-10-115

Section
V. Application Review Information

1. Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall Impact - Overall

Reviewers will provide an overall impact/priority score to
reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of
the following review criteria and additional review criteria (as applicable for
the project proposed).

Is the application reflective of a cohesive and integrated
unit, and is the integration evident within each of the components and across
the entire CTU?

Considering the overall goals, plans, and approaches
outlined in the CTU Research Overview in Component 1, in conjunction with the
specific information in Components 2-10, are the proposed size (including
number of CRSs), composition and structure of the CTU well justified and
adequate to address the scientific areas of the proposed clinical research
network(s)?

Are there strong and meritorious organizational, management,
and communication plans within the CTU?

Is the application reflective of approaches for efficient
utilization of resources and infrastructure, avoidance of redundancies, and
cost containment measures?

Does the application reflect a strong, robust culture of
quality management throughout all parts of the CTU?

Overall Impact – CTU Research Overview (Component 1)

Reviewers will provide an overall impact/priority score to
reflect their assessment of the likelihood for the CTU to exert a strong
sustained coordinated support of the NIAID HIV/AIDS Networks and the scientific
research agendas, in consideration of the following review criteria.

Scored Review Criteria - Component 1

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Does the application describe a cohesive structure
and range of support services to accommodate the scientific agenda for the
proposed NIAID HIV/AIDS network leadership groups?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New
Investigators, or in the early stages of independent careers, do they have
appropriate experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If the
project is collaborative or multi-PD(s)/PI(s), do the investigators have
complementary and integrated expertise; are their leadership approach, governance
and organizational structure appropriate for the project?

Do the PD(s)/PI(s), collaborators, and other
researchers have appropriate scientific knowledge and research experience to
contribute to the development of the clinical research network plans for which
they propose to affiliate?

Do the PD(s)/PI(s) have adequate qualifications,
experience, level of commitment, and availability to lead and coordinate the
CTU and its component parts?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented?
If the project is in the early stages of development, will the strategy
establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?

Is there a cohesive, integrated plan across the CTU
that addresses integration of functions within each of the scientific areas
proposed?

Do the CTU structure, management and governance allow
for rapid reconfiguration and access to resources in order to accommodate
changes to the scientific agenda for the proposed NIAID HIV/AIDS clinical
research network(s)?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Review Criteria– Components 2-10

Reviewers will evaluate the strengths and weaknesses
of the scientific and technical merits of application Components 2-10 according
to the following review criteria. However, separate scores will not be provided
for Components 2-10. Reviewers will consider the scientific and technical
merits of Components 2-10 in the development of an Overall Impact/Priority
Score for the application.

For
CTU Administration (Component 2), reviewers will consider:

Are the organizational structure, management plan and
lines of authority clear and appropriate with respect to the size and scope of
the CTU?

Do the key personnel have adequate qualifications,
experience, level of commitment, and availability to support and conduct CTU
activities?

Does the PD(s)/PI(s) have adequate organizational and
management experience to lead the proposed CTU?

Are there innovative approaches for the efficient
utilization and sharing of resources, and/or other cost containment measures
that support the proposed CTU configuration?

Is there sufficient institutional support for the CTU
in terms of space, position(s), administrative assistance, and other resources
that support CTU operations?

Is the financial management structure, including the
duties, responsibilities, experience, and time commitment of essential staff
adequate, with respect to the size and scope of the CTU?

In order to accomplish CTU goals, are appropriate
fiscal management plans and processes proposed to establish consortia
agreements, to allocate resources/protocol funds in a transparent manner, and
to provide financial reports to NIAID and the LOCs?

Are the criteria used to assess CRS capability to
receive protocol funds directly from the Network LOC appropriate?

For
Communication (Component 4), reviewers will consider:

Are there appropriate and feasible plans for
effective communication between the CTU and clinical research networks, NIAID
and other key groups?

Are there adequate plans for effective communication
across all components of the CTU, especially the performance sites?

For
Evaluation (Component 5), reviewers will consider:

Does the applicant propose appropriate and feasible
procedures to measure and assess the performance, productivity and capacity of
the CRSs?

Is there an adequate process for assessing and
preparing sites (including PS site(s), if appropriate) for protocol
implementation?

Are the plans to improve inadequate performance of
CTU component parts both appropriate and feasible?

For
Community (Component 6), reviewers will consider:

Is there an existing partnership, or are there
adequate, appropriately documented plans for developing such a partnership with
the community, to effectively engage the community including the Community
Advisory Board(s) in site activities?

Does the proposed CAB structure adequately represent
the communities from which the research will be conducted?

Is the plan for training CAB members adequate?

Are the proposed CAB processes adequate and
efficient?

Is there evidence that CTU personnel have the ability
to interact with the community in linguistic and culturally appropriate ways?

Is the plan for funding CAB activities adequate and
transparent?

For
Pharmacy (Component 7), reviewers will consider:

Do the essential pharmacy personnel at each
identified pharmacy have adequate qualifications (pharmacy education, training
and experience) and level of commitment to perform the day-to-day study product
management activities?

Are there acceptable facilities (including location,
infrastructure, equipment and adequate space) for study product management that
will ensure the integrity of the study products required for the range of
activities of the proposed NIAID HIV/AIDS clinical research networks?

Does the pharmacy have appropriate policies and
procedures for study product management in accordance with applicable
regulations or a system in place to develop and implement them?

Are there strong and appropriate plans for pharmacy
QA/QC and for training and mentoring of new pharmacy staff?

In support of the proposed pharmacy configuration,
are there innovative plans to share and efficiently use resources, and to
contain costs?

Is there evidence demonstrating strong past pharmacy
performance and experience?

For
Laboratory (Component 8), reviewers will consider:

Is the plan for ensuring quality local laboratory
operations and effective interactions with local laboratories and the LC
adequate?

Do the essential laboratory personnel at each
identified laboratory facility have adequate training, qualifications,
experience, level of commitment, and availability?

Are there appropriate measures for laboratory QA/QC,
participation in external quality assurance programs, adherence to GCLP and
adherence to regulatory agency guidelines?

Are the plans for maximizing organization efficiency
and effectiveness adequate and do they include sharing of laboratory resources,
harmonization of laboratory activities, and cost containment procedures?

Is there evidence demonstrating strong past
laboratory performance and experience?

For
Other Clinical Research Activities (Component 9), reviewers will consider:

Is the process for submitting protocols and timeline
for approvals through the proposed regulatory infrastructure (e.g.; IRB or
Ethics Committees) reasonable and adequate to support the breadth of activities
across all parts of the CTU?

Are innovative approaches to addressing any
regulatory challenges described?

Is there an adequate plan for ensuring regulatory
compliance across all parts of the CTU?

Are the infrastructure and plan for performing data
management activities adequate to ensure the accuracy and integrity of the
data?

Is the plan for quality management appropriate given
the size and scope of the CTU?

Is the plan for interactions between the SDMC and
local data management staff adequate?

Are there well described and adequate plans for staff
training and mentoring across all CTU components to support and conduct CTU
activities?

For
Each Clinical Research Site (Component 10), reviewers will consider:

With respect to the size and scope of the CRS, are
the organizational structure, management plan and lines of authority
appropriate and clear to ensure effective leadership and oversight of the CRS
activities?

With respect to the size and scope of the CRS, does
the organizational structure reflect adequate leadership and management
experience, level of commitment, and availability of proposed staff?

Does the CRS Leader have adequate leadership and
management experience to manage the proposed CRS?

Are there adequate staff with appropriate
qualifications and experience to recruit, screen, enroll, follow, retain, and
provide the required clinical care?

Based on demographic characteristics and the
incidence and prevalence of HIV/AIDS, is there strong documentation for the
availability and the appropriateness of the potential participant cohorts to
address the research agenda of each proposed clinical research network?

Are there strong plans for, and a documented ability
to recruit and retain research participants drawn from population(s) required
for the proposed clinical research?

Are there adequate, available, and appropriate
facilities to recruit, screen, enroll, follow, retain and provide the clinical
care required for the proposed research areas?

Is there evidence of innovative approaches to sharing
and efficient utilization of resources, or other innovative cost containment
measures that support the proposed CRS?

For
the Optional Clinical Research Network on Antibacterial Resistance (Component
11), reviewers will consider:

The capacity and capability of the CTU to perform
clinical trials on antibacterial resistance will not receive a technical merit
score. However reviewers will evaluate the strengths and weaknesses of the
scientific and technical merit of optional Component 11 according to the
following points. This evaluation of optional Component 11 will not be
factored into the Overall Impact score for the CTU application.

Is there evidence of the ability to recruit and
retain appropriate subjects for antibacterial resistance clinical research or
trials?

Is there evidence of the ability to identify,
recruit, and manage appropriate CRS for antibacterial resistance clinical
research or trials?

Is there evidence of experience monitoring progress
toward enrollment goals and ability to adjust the number of clinical sites
(increase or decrease)?

Response
to this optional component will not affect the overall impact/priority score
for the application.

Additional Review Criteria - Overall

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact/priority score, but will
not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of
minorities and members of both genders, as well as the inclusion of children. For
additional information on review of the Inclusion section, please refer to the Human
Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the following
five points: 1) proposed use of the animals, and species, strains, ages, sex,
and numbers to be used; 2) justifications for the use of animals and for the
appropriateness of the species and numbers proposed; 3) adequacy of veterinary
care; 4) procedures for limiting discomfort, distress, pain and injury to that
which is unavoidable in the conduct of scientifically sound research including
the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable
restraining devices; and 5) methods of euthanasia and reason for selection if
not consistent with the AVMA Guidelines on Euthanasia. For additional
information on review of the Vertebrate Animals section, please refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable.

Renewals

For Renewals, the committee will consider the
progress made in the last funding period. .

Revisions

Not Applicable.

Additional Review Considerations - Overall

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions that exist
in other countries and either are not readily available in the United States or
augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s),convened by the NIAID in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall
impact/priority score.

Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response
to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center and will compete for available funds with all
other recommended applications submitted in response to this FOA . Following initial peer review, recommended applications will receive a second level of
review by the National Advisory Allergy and Infectious Diseases Council l. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

Geographical distribution of CRSs

Scientific Leadership Diversity

The NIAID reserves the right to conduct site visits or
reverse site visits prior to award when deemed essential.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the
PD(s)/PI(s) will be able to access his or her Summary Statement (written
critique) via the eRA Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS)
grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is
applicable when State and local Governments are eligible to apply), and other
HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the
cooperative agreement, an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH programmatic
involvement with the awardees is anticipated during the performance of the
activities. Under the cooperative agreement, the NIH purpose is to support and
stimulate the recipients' activities by involvement in and otherwise working
jointly with the award recipients in a partnership role; it is not to assume
direction, prime responsibility, or a dominant role in the activities.
Consistent with this concept, the dominant role and prime responsibility
resides with the awardees for the project as a whole, although specific tasks
and activities may be shared among the awardees and the NIH as defined below.

Responsive applications will serve as Clinical Trials Units
focused on the following clinical research networks:

Clinical Research Network on Therapeutics for HIV/AIDS and
HIV-associated Infections in Adults

Clinical Research Network on HIV/AIDS and HIV-associated
Infections in Pediatric and Maternal Populations

Clinical Research Network on Integrated Strategies to Prevent HIV
Infection

Clinical Research Network on Microbicides to Prevent HIV
Infection

Clinical Research Network on HIV Vaccines to Prevent HIV
Infection

Clinical Research Network on Antibacterial Resistance

CTU
PD(s)/PI(s) will have primary responsibility forthe overall
activities and performance of the CTU, including, but not limited to:

Execution of the research agenda of the clinical research
network(s).

Coordination and collaboration with the LG to ensure performance
monitoring and evaluation of sites.

Knowledge, acceptance and compliance by all CTU component parts
with the policies, procedures and bylaws of the NIAID clinical research
network(s), including: Network policies and procedures for the collection,
recording, storage and reporting of clinical trial data, sharing of research
data and research resources, the research priorities of the NIAID and the
affiliated networks; and performance standards established by the NIAID and the
affiliated networks.

Ensuring implementation of clearly defined organizational and
communication plans and standard operating procedures to ensure close
supervision and oversight of the day-to-day activities of the CRS (and PS site(s),
if applicable).

The receipt and appropriate administration of core funding to
establish and maintain a minimal level of clinical research activities.

The receipt and appropriate administration of protocol funding
provided by either NIAID or the clinical research network(s). The CTU PD(s)/PI(s)
will ensure that timely and accurate financial reports for all CTU component
parts are provided to the NIAID and the clinical research network(s). This
information must be part of the annual progress report, or as requested, to
NIAID and under separate cover sent to each affiliated network LOC.

Ensuring compliance with all Federal regulations for human
subjects, investigational agents and devices, and NIH and NIAID policies and
procedures. NIAID-sponsored clinical research cannot be initiated at any CRS
without prior approval by NIAID. All CRS(s) are also required to complete Protocol
Registration for all clinical protocols in accordance with current NIAID
policy and procedures prior to study initiation.

Ensuring compliance with the NIAID and clinical research
network(s) laboratory standards including participation in Quality Assurance
(QA) programs and maintaining appropriate certification.

Developing and implementing strategies at each CRS (and PS
site(s), if applicable) for the recruitment, screening, enrollment, retention
and long-term follow-up of study participants appropriate to the conduct of the
proposed research. The PD(s)/PI(s) must ensure that priority is placed on
recruiting participants who are representative of the populations most impacted
by HIV/AIDS (or antibacterial resistance if applicable) within their
geographical region, paying particular attention to gender and members of
minority groups.

Ensuring that the CTU develops, implements, and oversees a
comprehensive Quality Management Plan for all parts of the CTU in order to
continually assess the quality of the research records and activities to ensure
compliance with all Federal regulations, International Conference on
Harmonisation Good Clinical Practice (ICH GCP) guidelines, and NIH policies
regarding participant safety, data completeness, accuracy, and quality
assurance.

Ensuring cooperation with the NIAID Clinical Site
Monitoring/Auditing representatives, and any other NIAID authorized groups. The
purpose will include but not be limited to the review of research records and
activities to verify compliance with protocol requirements, all applicable U.S.
Federal regulations, ICH GCP guidelines, and NIH policies on participant
safety, data completeness and accuracy, and quality control. All performance
problems identified through clinical monitoring must be evaluated in a timely
manner and a plan for resolution developed, implemented, and documented, with
emphasis on ensuring that the issue should not re-occur.

Implementation of a plan to achieve meaningful community
partnership in CTU activities. This must include one or more Community Advisory
Boards (CABs) to represent the local population(s) impacted by HIV/AIDS. The
CTU must have procedures to ensure the community is engaged in the research
process; provide financial and technical assistance from appropriately trained,
culturally sensitive and experienced staff to support CAB activities and
training; foster a partnership between researchers and the community, including
the sharing of research results with the community, and develop ways to assess
these efforts.

Compliance with all adverse event reporting requirements
designated by the NIAID and clinical research network(s), including, but not
limited to the established policies and procedures delineated in the "Expedited
Adverse Experience Reporting Manual”.

Ensuring that the CTU provides information requested by NIAID or
affiliated clinical research network(s) in a timely manner. In addition to
clinical trial data, routine and ad hoc reports may be required. These reports
may include, but not be limited to, participant recruitment and retention
rates, summary demographic profiles of study participants, timeliness and
completeness of all data, completeness and quality of laboratory data, and
administrative and financial reports.

Ensuring compliance with the policies and procedures set forth by
the clinical research network(s) and the NIAID regarding presentation and
publication of major findings in the scientific literature. Awardees will
retain custody of and have primary rights to the data and software developed
under these awards, subject to Government rights of access consistent with
current HHS, PHS, and NIH policies.

Ensuring effective leadership, clear lines of authority, strong
communication pathways, and appropriate oversight for all parts of the CTU.

NIH
will have substantial programmatic involvement that is above and beyond the
normal stewardship role in awards, as described below:

NIAID and other NIH co-sponsors of the Leadership Groups will
have substantial scientific and programmatic involvement during the conduct of
this activity, through establishing the research agenda, and providing
technical assistance, advice, and coordination. The role of the NIH staff, as
described throughout these terms of cooperation, is to assist and facilitate
the activities necessary to execute the research agenda, not to direct the
specific research. NIH staff will interact directly with the CTU PD(s)/PI(s),
as well as the clinical research network(s) LOC, SDMC, and/or LC PD(s)/PI(s),
and any other collaborating institutions as needed.

Program
Official: Staff assistance will be provided by a NIAID Program
Officer. These NIAID staff members will have substantial
scientific/programmatic involvement during the conduct of this activity through
technical assistance, advice and coordination above and beyond the normal
program stewardship role for grants:

Assure that network research efforts are consistent with that of
the NIAID agenda for clinical research, and complement those of other NIH and
NIAID programs.

Facilitate coordination among the NIAID- and other NIH-supported
clinical trials networks, and research groups, and other U.S. Government
agencies promoting collaborations and facilitating information exchange.

Communicate the NIAID scientific priorities.

Track protocol development, implementation, and study conduct.

Attend and interact at meetings, trainings, and conference calls.

Serve as resources for scientific and policy information.

Organize meetings to facilitate exchange of information,
including network meetings.

Oversee contract resources that facilitate the provision of
investigational agents or to meet needs identified by the NIAID Strategic
Working Group (SWG) or other advisory bodies.

Participate in the presentation of research results, including
publications.

Oversee use of discretionary funds such as PF and Administrative
Supplemental support;

These staff will be identified at the time of award and
their roles and responsibilities will be addressed in the NOA.

NIAID
will serve as a liaison between pharmaceutical companies, the
FDA, and clinical research network(s) investigator(s) and/or partners. In
accordance with NIH policy, NIAID will ensure that all clinical trials
performed through the CTU are conducted in accordance with ICH GCP and
applicable Federal regulations.

Clinical
Site Oversight. The NIAID will review and approve all CRS(s)
(and PS site(s), if appropriate) prior to initiation of any NIAID-sponsored
clinical research. NIH staff may conduct site visits to the CTU or component
parts for the purposes of assessing site readiness, or to evaluate ongoing
operations, clinical research processes and recordkeeping, or to investigate
significant findings on monitoring or other Network LOC/LG reports. The NIAID
staff or designee will also review site visit reports and reserves the right to
independently monitor the CRS(s) in accordance with FDA/ICH guidelines. In
collaboration with the clinical research networks, NIAID reserves the right to
temporarily suspend a trial at a CRS based on pervasive, significant
noncompliance.

Study
Product. For studies in which the NIAID is the IND or IDE
sponsor, the NIAID staff and/or contractors will provide consultation with CTU
staff on study product-related issues including manufacturing, preparation,
administration and availability of active dosage forms and placebo. Pharmacy
Establishment Plans identifying the Pharmacist of Record, describing the
policies and procedures for the safe and proper use of study products, and the
study product control system, including technical procedures for product
ordering, control, dispensing, and accountability are required. The NIAID staff
and/or contractors may also:

interact with pharmaceutical company collaborators to facilitate
adequate and timely supply of product;

oversee the distribution of study product to the CRS (and PS
sites, if appropriate) conducting the study.

Training. The NIAID will provide a variety of training activities to help
ensure that consistent standards for protection of human subjects, conduct of
clinical trials, and documentation are achieved. This training may be developed
in conjunction with clinical research network(s) and be provided directly by
the NIAID staff or through contractors. Training areas will include, but not be
limited to, regulatory requirements, GCP, adverse event reporting, quality
management, human subject protections, and NIAID policies and procedures. Some
training or retraining may require mandatory attendance.

Safety
Reports. For studies in which the NIAID is the IND or IDE
sponsor, the NIAID will assume responsibility for the reporting of safety
information in accordance with FDA requirements and preferences. In order to
provide for consistent reporting of serious adverse experiences across clinical
trials groups, the NIAID shall provide current policies and procedures that
govern the reporting of adverse events in NIAID-sponsored trials. The NIAID
staff and/or contractors will provide training in the specific procedures and
requirements for adverse event reporting for clinical trials conducted under
this award.

Protocol
Development. NIAID staff who will participate in the
development of selected clinical research protocols include:

Medical and Program Officers who will provide clinical and
scientific expertise.

Pharmacists who will participate on Network protocol teams and
consult on pharmaceutical aspects, available dosage forms, and placebos.

Protocol
Approval. NIAID will review and must approve all protocols
prior to protocol implementation.

Safety
Monitoring. NIAID staff will participate in the development of
appropriate safety monitoring plans for all planned clinical trials and must
approve the plan for all trials involving investigational drugs, devices, or
biologics and other clinical research perceived to involve more than a minimal
risk. The frequency and intensity of safety monitoring will be based on
individual study characteristics and past experience with study products and
may require review by an Independent Safety Monitor, Independent Monitoring
Committee (IMC), Safety Monitoring Committee (SMC) or Data and Safety
Monitoring Board (DSMB). NIAID Medical Officers will be part of
network-organized protocol safety review teams to monitor the safety and efficacy
of the intervention(s) for ongoing studies, and will be provided with
appropriate reports. Approval of the final monitoring plan, including the
composition of the review committee, by NIAID is required prior to study
initiation. NIAID independently supports DSMBs that oversee Phase IIb/III and
other select clinical trials at the discretion of NIAID.

Study
Termination. The NIAID reserves the right to terminate or
temporarily suspend the participation of a CRS (and PS site(s), if appropriate)
in a clinical study for any of the following reasons:

risk to subject safety;

failure to comply with Good Clinical Practice, federal
regulations, or Terms of Award;

risks that cannot be adequately quantified;

ethical concerns raised by the local community or local medical
care/health care authorities;

failure to remedy deficiencies identified by site monitoring
teams; and

failure to meet NIAID and clinical research network performance
standards

Access
to Data. The awardees retain the rights to the data, consistent
with current DHHS, PHS, NIH and NIAID policies; however, NIH will have access
to all data generated (raw and analyzed) and may periodically review it. This
includes a review of data as recorded on the case report forms or in the
central database, and external checking against the original source
documentation as required by federal regulation and NIAID as the IND sponsor.
NIAID may request from the CTU specific data analysis needed for programmatic
activities or for issues related to NIAID plans with other partners. The NIH
may provide public access to selected data sets generated with the use of
public funds within a reasonable time after the primary analysis and
publication. NIAID will develop a memorandum of agreement with the
owners/providers of applications/systems that share data/information with the DAIDS-ES.

Performance
Assessment. NIAID in conjunction with the clinical research
network(s) will assess the performance of all components of the CTU in an
ongoing manner. Each clinical research network will develop an evaluation plan
with defined goals and measurable objectives linked to specific performance
metrics as appropriate to the network clinical research area(s) and include
remedial actions for sites failing to meet acceptable standards. Each CTU is
expected to adhere to the performance standards of the networks with which they
propose affiliation. CTU components that fail to meet performance standards
may be subject to withdrawal of funding.

Areas
of Joint Responsibility:

Execution of this program will require collaboration among
the CTU PD(s)/PI(s), the NIAID staff, the Network LG and other co-sponsoring
NIH Institutes and Centers. Specific tasks and responsibilities in carrying out
the activity will be shared among the awardee, NIAID staff, Network staff, and
NIAID contractors as described above.

External
Advisors. NIAID in conjunction with the clinical research
network(s) will seek evaluation, advice and recommendations concerning ongoing
and planned research activities from external advisory groups. Such review
activity may occur through the advisory working group's attendance at a regular
network meeting organized by the LOC, and/or at separate meetings arranged by
NIAID. CTU investigators will participate in these reviews with support for
attendance provided through the LOC budget, and will provide written materials
and oral presentations regarding the status of ongoing research activities, future
plans (including proposed new research activities/investigators), and plans to
curtail, discontinue and/or modify current research activities.

Dispute Resolution:

Any disagreements that may arise in scientific or
programmatic matters (within the scope of the award) between award recipients
and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel
will be convened. It will have three members: a designee of the Steering
Committee chosen without NIH staff voting, one NIH designee, and a third
designee with expertise in the relevant area who is chosen by the other two; in
the case of individual disagreement, the first member may be chosen by the
individual awardees. This special dispute resolution procedure does not alter
the awardee's right to appeal an adverse action that is otherwise appealable in
accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45
CFR Part 16.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH
Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants
Policy Statement for additional information on this reporting requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and
under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.